POS1348 PATIENTS WITH VEXAS DIAGNOSED IN A DANISH TERTIARY RHEUMATOLOGY SETTING HAVE HIGHLY ELEVATED INFLAMMATORY MARKERS, MACROCYTIC ANEMIA, AND NEGATIVE AUTOIMMUNE BIOMARKERS.
Authors: M. Nyhuus Bendix Rasch, F. Szabados, J. M. B. Jensen, K. O. Nielsen, E. M. Hauge, A. Troldborg
Journal: Annals of the Rheumatic Diseases (2022)

Background VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome was described in 2020 with overlapping features of rheumatology and hematology. VEXAS is an autoinflammatory condition caused by somatic mutations in the UBA1 gene at methionine-41. As patients present with highly variable clinical symptoms [1], their path in the clinical system is often complicated, and characterized by many strenuous examinations and biopsies. It is pivotal, that we familiarize with the VEXAS phenotype and advance identification of patients with VEXAS. Objectives We aimed to characterize patients diagnosed with VEXAS in a tertiary rheumatology referral center since December 2020 when the syndrome was described [2]. Methods All patients were identified and diagnosed at the department of Rheumatology, Aarhus University Hospital (AUH), Denmark. Patients underwent testing for the UBA1 somatic mutations using sanger sequencing at the department of Clinical Immunology, AUH. Sequencing analyzed for somatic variants in/at exon 3 (NM_003334.4: c.118-1G&gt;C, c.121A&gt;C/G, c.122T&gt;C og c.167C&gt;T). Clinical and biochemical data were retrieved from the hospital electronic patient chart. Continuous variables are presented as median with interquartile range (IQR) and categorical variables as percentages. Results A total of 11 male patients with clinical suspicion of VEXAS underwent sequencing. Five men were identified in the period December 2020 to December 2021 with UBA1 somatic mutations. Median age at diagnosis was 84 (75-87). Symptoms debuted on average 22 months (IQR 20-40) before diagnosis. All patients had significantly elevated markers of inflammation: median CRP 297 (196-386), IL-2-receptor, and ferritin and presented with macrocytic anemia. None of the patients were positive for autoimmune biomarkers like ANA, ACPA, MPO-, or PR3-ANCA. Conclusion This is, to the best of our knowledge, the first report of Danish patients with the VEXAS syndrome. Patients are males with persistent inflammation, constitutional symptoms, and heterogeneous clinical presentations. Common features for all patients in this study were highly elevated inflammatory markers, macrocytic anemia, and negative autoimmune biomarkers. References [1]Georgin-Lavialle et al . Br J Dermaol. 2021 Oct 1. Online ahead of print [2]Beck et al . N Engl J Med. 2020 Dec 31;383(27):2628-2638. Table 1. Clinical, biochemical characteristics at diagnosis and treatment of Danish VEXAS patients. Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Total n(%) or median (IQR) Clinical characteristics Age at diagnosis 73 89 77 84 85 84 (75-87) Time from symptom onset till diagnosis (months) 18 21 47 30 22 22 (20-40) UBA1 variant c.122 T&gt;C p.Met41Thr c.122 T&gt;Cp.Met41Thr c.122 T&gt;Cp.Met41Thr c.121 A&gt;Cp.Met41Leu c.118-1 G&gt;Cp.(splice) Macrocytic anemia + + + + + 5 (100%) CRP(max, mg/ml) +(335) +(436) +(220) +(172) + (297) 5 (100%) (297 (196-386)) Constitutional symptoms* + + + + + 5 (100%) Vasculitis + + + - + 4 (80%) Chondritis - - + - + 2 (40%) Ocular inflammation - - + - - 1 (20%) Arthritis + - + + - 3 (60%) Lung involvement - + + + + 4 (80%) Proteinuria - + + - + 3 (60%) Thrombosis + - - + - 2 (40%) BM vacuoles - + + NA - 2/4 (50%) Biochemical characteristics ANA - - - - - 0 (0%) ACPA NA - - - NA 0 (0%) PR3 or MPO-ANCA - - - - - 0 (0%) IQR: inter quartile range, BM: bone marrow, ANA: anti-nuclear antibodies, ACPA: anti-citrullinated protein antibody, PR3-ANCA: proteinase-3 anti-cytoplasmatic antibody, MPO: myeloperoxidase, NR: within normal range, NA: not available.*Constitutional symptoms (fever, night sweats, weight loss). Disclosure of Interests Mads Nyhuus Bendix Rasch Speakers bureau: Speakers fee in context of alignment meeting in autoinflammatory diseases by Sobi, Fruzsina Szabados: None declared, Jens Magnus Bernth Jensen: None declared, Kirstine Overgaard Nielsen: None declared, Ellen-Margrethe Hauge Speakers bureau: Has received fees for speaking and/or consulting from AbbVie, Sanofi, Sobi, MSD, UCB, Consultant of: Has received fees for speaking and/or consulting from AbbVie, Sanofi, Sobi, MSD, UCB, Grant/research support from: Research funding to Aarhus University Hospital from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Roche, Novartis;, Anne Troldborg: None declared